Stents have become the treatment of choice for a variety of blood vessel diseases in humans and are in common use worldwide. From the beginning of their use, it is known that an unacceptable percentage of cardiac stents become blocked after installation. This restenosis is a serious health problem: a patient may be more seriously impaired after treatment than before. Restenosis occurs when smooth muscle cells in the blood aggregate into clumps and cause the stent to become occluded. Drug-eluting coatings have been used to prevent clumping. Based on current data, it now appears that these coatings are not a satisfactory solution. For example, coated stents have been shown to cause blood clots several years after installation (Brian Vastag, “Stents Stumble,” Science News, Jun. 23, 2007 Vol. 171, pp 394-395). A patient receiving a coated stent must use blood thinners to prevent formation of blood clots that may dislodge from the region of the stent and cause stroke or heart attack. If the blood thinning treatment is interrupted, the probability of stroke is greatly increased. Thus, coated stents have therefore proved not to be a viable solution to the problem of stent restenosis.
It has recently been proposed that the restenosis of a stent is largely determined by whether the first layer of cells to grow on the surface of a stent are endothelial cells or smooth muscle cells (Julio Palmaz, Lecture at SMST conference 2003, Asilomar Calif. Comments not included in Proceedings of the conference). Described herein are stent covers which selectively enable endothelial cells to grow on their surface in comparison to smooth muscle cells, as well as methods of manufacturing and using them.
Other methods of preventing restenosis have been developed. For example, Palmaz describes a method using chemical affinities (resulting from charges on the surface of the stent) to regulate the growth of endothelial cells versus smooth muscle cells. U.S. Pat. No. 6,820,676 to Palmaz et al. teaches the use of surface relief patterns corresponding to crystal boundaries in metal to the enhance growth of cells. However, these patterns are irregular in size and shape and so are not ideally selective for a specific protein. In WO07078304A2, Dubrow et al. suggest using fibers (e.g., nanofibers or nanowires) to form a substrate for use in various medical devices.
Stents using shape memory alloys (e.g., Nitinol) to form thin-film stent covers are currently being developed. For example, US 2008/0161936 to Feller et al. describes a stent including a thin-film of shape memory alloy having different porosities in the deployed and undeployed configurations. A stent cover is typically placed over a stent to provide protection against debris that may be dislodged during installation of the stent. Described herein are stents or stent covers including a thin film coating or surface that preferably selects endothelial cells (e.g., from the blood stream) to grow on the inside surface of a thin-film stent or stent cover compared to other cell types (e.g., smooth muscle cells). This may be accomplished by forming nanostructures on the inside of the stent or stent cover. These nanostructures may be formed of one or more layers, and may correspond to recurring patterns on endothelial cell membrane proteins. Endothelial cells that come in contact with the surface nanostructures may selectively adhere to them. For example, endothelial cells (as opposed to smooth muscle cells) may ‘recognize’ the surface structure by pattern matching (or pattern recognition) and adhere. This pattern recognition step is a key element in many molecular biology processes. The devices and methods described herein take advantage of this native molecular biological process (e.g., cell-surface interactions) to influence the adherence of one type of cell (e.g. endothelial cells) in preference to other types (e.g. smooth muscle cells). Thus, surface nanostructures may be used to selectively enhance adhesion of endothelial cells over smooth muscle cells.